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Biomedical subjects

L Fisher

Publications and source records attributed to L Fisher.

At least 163 records · Page 9Linked to original sources
PubMed1989

Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay.

A Y-chromosome-specific in situ hybridization assay was used to assess the frequency with which host bone marrow cells are retained after marrow grafting. The majority of patients (74%) showed the presence of both host and donor marrow cells when assayed 14 days after transplant. By 84 days posttransplant only 4% of the patients retained host marrow cells. Only 1 of 19 evaluable patients analyzed over 1 year posttransplant showed minimal retention of host cells. No statistical correlation was found between retention of host cells posttransplant and the development of relapse or acute or chronic graft-versus-host disease. Pretransplant conditioning regimen, HLA-matching, diagnosis, disease status at transplant, ABO-matching, and patient age also showed no correlation with the retention of host cells posttransplant.

Bone Marrow Cells↗
PubMed1989

Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia.

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.

Bone Marrow Transplantation↗
PubMed1989

Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms.

The occurrence of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation for leukemia is thought to decrease the probability of recurrence. To study this effect (called adoptive immunotherapy) we modified the prophylaxis of GVHD in patients with advanced hematologic neoplasms (mostly leukemia) who received bone marrow transplants. Patients under 30 years of age were randomly assigned to one of three regimens of post-transplantation immunosuppression: Group I (n = 44) received a standard course of methotrexate for 102 days after transplantation, Group II (n = 40) received an abbreviated (11-day) course of methotrexate, and Group III (n = 25) received the standard course of methotrexate plus viable buffy-coat cells from the marrow donors. All 109 patients received cyclophosphamide (60 mg per kilogram of body weight on each of two days), total-body irradiation (2.25 Gy daily for seven days), and unmodified marrow from HLA-identical sibling donors. The frequency of GVHD of Grades II through IV was 25 percent in Group I, 59 percent in Group II, and 82 percent in Group III (P = 0.0001). The incidence of chronic GVHD, however, did not differ significantly among the groups (33, 51, and 44 percent, respectively), nor did the five-year probability of recurrence of disease (38, 45, and 33 percent, respectively). However, mortality from causes other than cancer was 34 percent in Group I, 45 percent in Group II, and 64 percent in Group III (I vs. III, P = 0.024); the deaths were due primarily to infections complicating the course of GVHD. With a median follow-up of 5.1 years (range, 3.9 to 7.4), disease-free survival was 41 percent in Group I, 30 percent in Group II, and 24 percent in Group III (the differences were not statistically significant). We conclude that abbreviating methotrexate prophylaxis or infusing donor buffy-coat cells increased the incidence of acute GVHD and related mortality without altering the incidence of chronic GVHD or the recurrence of malignant disease.

Adolescent↗
PubMed1989

Sucrose-regulated expression of a chimeric potato tuber gene in leaves of transgenic tobacco plants.

Patatin is a family of lipid acyl hydrolases that accounts for 30 to 40% of the total soluble protein in potato tubers. Class-I patatin genes encode 98 to 99% of the patatin mRNA in tubers, but are not normally expressed in other tissues. They are not totally 'tuber-specific'; however, since they can be induced to express at high levels in other tissues under conditions of sink limitation or in explants cultured on medium containing elevated levels of sucrose. To examine the evolution of the mechanisms that regulate patatin gene expression, we introduced a chimeric patatin-beta-glucuronidase (GUS) gene containing 2.5 kb of 5' flanking sequence from the Class-I potato patatin gene PS20 into tobacco plants. The construct was not expressed at significant levels in leaves of juvenile plants or plantlets cultured in vitro, but was expressed at high levels in explants cultured on medium containing 0.3 to 0.4 M sucrose. While there were differences in the expression of the chimeric gene between transgenic tobacco and potato plants, the pattern of sucrose induction was very similar. These results suggest that the mechanism that controls patatin gene expression in potato tubers evolved from a widely distributed mechanism in which gene expression is regulated by the level of available photosynthate.

Carbohydrates↗
PubMed1989

Comparison of coronary angioplasty with medical treatment for single- and double-vessel coronary disease with left anterior descending coronary involvement: long-term outcome based on an Emory-CASS registry study.

The 3 to 5-year clinical outcomes of 627 consecutive patients selected for treatment with percutaneous transluminal coronary angioplasty (PTCA) at Emory University Hospital for one- or two-vessel coronary artery disease with involvement of the left anterior descending coronary artery, between July 1981 and June 1983, and 865 patients in the Coronary Artery Surgery Study with similar coronary artery disease involvement selected for medical therapy between 1975 and 1979 were compared. Cox analyses and stratified life table analyses were used to adjust for differences in 13 variables including concurrent medical therapy. Complete follow-up was obtained in 97% of PTCA patients and 99% of medically treated patients. After correction for baseline differences in significantly predictive variables, there was no difference between the relative risk of death after PTCA vs medical therapy (RR = 0.7; p = 0.36). However, results of analysis of prospectively defined subsets showed a potential survival benefit after PTCA for patients with an ejection fraction less than 50% (RR = 0.2; p = 0.02) and also for patients with two-vessel disease (RR = 0.2; p = 0.04). For the groups as a whole there was no difference in risk of infarction after PTCA and medical therapy (RR = 0.8; p = 0.58). However, for patients with 90% to 99% LAD stenosis there was a trend toward lessened risk of infarction after PTCA (RR = 0.6; p = 0.15). No patient subset had a higher risk of death or infarction with PTCA (p less than or equal to 0.15). The likelihood of later surgery was increased after PTCA (RR = 1.5; p = 0.002). Angina, employment, and activity levels were improved after PTCA. Thus PTCA compared to medical therapy was associated with improved functional status and may decrease the risk of death and infarction in certain patient subsets. However, bypass surgery was more often performed in patients initially treated with PTCA. These data should be interpreted in light of their nonrandomized study origin and generation from different clinical sites.

Activities of Daily Living↗
PubMed1989

Morphology of left anterior descending coronary territory lesions as a predictor of anterior myocardial infarction: a CASS Registry Study.

Despite a growing awareness of the correlation of coronary artery stenoses morphology with clinical syndromes, no comprehensive, prospective analysis of the implications of stenosis morphology on risk of myocardial infarction has been reported. Angiograms from 118 patients, representative of the 4.9% of medically treated Coronary Artery Surgery Study (CASS) patients who during subsequent 3 year follow-up study had an anterior myocardial infarction, were matched on the basis of arteriographic anatomy and disease with 141 patients who did not have an anterior infarction. Angiograms from these 259 patients with 557 left anterior descending artery stenoses were reviewed without knowledge of clinical outcome. Conditional regression analyses were performed to determine the importance of stenosis morphology, relative to computer-determined stenosis severity and other clinical variables, in the prediction of risk of infarction. Univariate analysis revealed luminal roughness (odds ratio 4.5; p = 0.001) and lesion length (odds ratio 1.7 per unit length; p = 0.007) to be highly correlated with future risk of infarction. Multivariate analysis revealed left anterior descending artery percent stenosis greater than or equal to 50%, lesion roughness, left circumflex artery stenosis and smoking, in that order, to be predictive of anterior myocardial infarction, whereas 22 other morphologic variables were not independently predictive of outcome. The importance of stenosis roughness may relate to its propensity for thrombogenesis and should be considered in clinical decision making.

Angiography↗
PubMed1989

Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1.

The definition of human immunodeficiency virus type 1 (HIV-1) immunogenic epitopes is central to the rational design of AIDS vaccine strategies. In this study, we have generated seven HIV-1 reverse transcriptase-specific cytotoxic T-lymphocyte (CTL) clones from the peripheral blood of two seropositive subjects. Epitopes recognized by these CTL clones were identified by using target cells infected with recombinant HIV-1-vaccinia virus vectors expressing truncated reverse transcriptase proteins and further defined by using target cells incubated with overlapping 25-amino acid synthetic reverse transcriptase peptides. Five different CTL epitopes were identified, and in each case recognition was restricted by class I human leukocyte antigens (HLA). Clones maintained specific cytolytic function in continuous culture for up to 11 months, requiring only periodic restimulation with a CD3-specific monoclonal antibody. These results indicate that HIV-1-specific, major histocompatibility class I-restricted CTL recognize multiple epitopes of a single viral gene product in conjunction with different host HLA antigens. In addition, they demonstrate that human virus-specific CTL can be grown in long-term culture without the need for reexposure to viral antigen.

Cell Line↗
PubMed1988

Prediction of risk of anterior myocardial infarction by lesion severity and measurement method of stenoses in the left anterior descending coronary distribution: a CASS Registry Study.

To assess the 3 year risk of anterior myocardial infarction in patients with left anterior descending coronary artery territory disease (30 to 100% stenosis), National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Surgery Study (CASS) registry patients were identified who were 1) medically treated, and 2) had evidence of viable anterior myocardium at the time of baseline angiography. Prospectively, 118 patients having an anterior infarction within 3 years of baseline angiography were identified from annual follow-up of 4,535 medically treated patients who had left anterior descending coronary artery disease and viable anterior myocardium. From the large residual pool of patients without infarction, 141 were randomly selected from a stratified matrix to represent the entire group. The maximal percent stenosis was estimated by the CASS multiple angiographers, by a current single observer rereading and by contemporary computer measurement techniques. Absolute lumen dimension was assessed by computer measurement. The 3 year risk of anterior infarction was 2% for patients with their most severe left anterior descending stenosis less than 50%, 6% for patients with one such stenosis greater than or equal to 50% and 11% for patients with two or more such stenoses greater than or equal to 50% (p less than 0.02). Stenoses of 90 to 98% had the highest (15%) 3 year risk of anterior myocardial infarction. The three methods used to measure maximal percent stenosis differed little with regard to their predictiveness. Absolute lumen dimension was less predictive of risk. These results may provide a more rational basis on which to base coronary revascularization decisions.

Clinical Trials as Topic↗
PubMed1988

Epstein-Barr virus lymphoproliferation after bone marrow transplantation.

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.

Acyclovir↗
PubMed1988

Cyclosporine v methotrexate for graft-v-host disease prevention in patients given marrow grafts for leukemia: long-term follow-up of three controlled trials.

One hundred seventy-nine patients with acute nonlymphoblastic leukemia in first remission (n = 75), chronic myelocytic leukemia in chronic or accelerated phase (n = 48) or leukemia in advanced stage (n = 56) were given HLA-identical marrow grafts and randomized to receive methotrexate or cyclosporine for prevention of graft-v-host disease (GVHD). The current report updates the three prospective trials with follow-ups ranging from 3.2 to 6.2 years after marrow grafting. Results were analyzed separately for each individual study and for all three studies combined. Overall, 40% of patients given cyclosporine and 55% of those given methotrexate developed acute GVHD (P = .13); the incidence of chronic GVHD was 42% and 48%, respectively (P = .67). Twenty-two percent of cyclosporine-treated patients and 30% of methotrexate-treated patients developed interstitial pneumonia of any etiology (P = .25), and the figures for cytomegalovirus pneumonia were 18% and 20%, respectively (P = .41). The overall incidence of leukemic relapse was 31% in cyclosporine-treated patients and 36% in methotrexate-treated patients (P = .75). The probabilities of survival for cyclosporine-v methotrexate-treated patients were comparable for all three study groups: 52% v 48% in patients with acute nonlymphoblastic leukemia (P = .42), 55% v 60% for those with chronic myelocytic leukemia (P = .61), 12% and 12% for those with advanced leukemia (P = .93), and 39% v 38% overall (P = .72). We conclude that cyclosporine and methotrexate are comparable regarding the likelihood of acute/chronic GVHD, interstitial pneumonia, leukemic relapse, and long-term survival.

Acute Disease↗
PubMed1987

Bombesin alters the sympathetic nervous system response to cold exposure.

The accumulation of dopamine in interscapular brown fat, heart, kidney and mesenteric white fat has been used as an index of sympathetic nervous activity in rats in which dopamine beta-hydroxylase has been blocked. Intracerebroventricular administration of bombesin impaired the cold-induced increase of dopamine accumulation in interscapular brown fat but not in other tissues. These studies provide evidence that bombesin acts within the central nervous system to modify efferent sympathetic nervous system responses to cold exposure in a viscerotopically specific manner. This action of bombesin is consistent with the other central nervous system actions of this peptide, i.e. inhibition of heat production and disruption of thermoregulation.

Adipose Tissue, Brown↗
PubMed1987

Natural killer cell and islet killer cell activities in human type 1 diabetes.

Peripheral blood mononuclear cells from 14 type 1 diabetic patients were examined for natural killer cell activity using the K562 cell line as 51Cr labeled targets. Mean cytotoxicity of K562 cells by unseparated mononuclear cells derived from new onset type 1 patients (12 +/- 1.6%) was lower (P less than .01) than that observed in non diabetic controls, (25 +/- 4.2%). Mean natural killer cell cytotoxicity mediated by enriched non-T cells from patients (41 +/- 5.8%) was also lower (P less than 0.03) than in the control group (56 +/- 3.7%). Specificity of these findings was evaluated by also examining other diabetic patient subgroups. Mean non T cell mediated natural killer cell activity in type 2 diabetic patients and type 1 patients with long term disease was 65 +/- 5.4% and 62 +/- 4.8% respectively (p less than 0.001 vs new onset type 1 patients). Longitudinal studies of new onset type 1 patients during the remission (honeymoon) phase revealed no improvement of impaired natural killer cell activity. In 30 new onset and 11 remission diabetic patients, mean non-T cell-mediated cytotoxicity was also measured using dispersed 51Cr labeled pancreatic islet target cells. Mean islet cytotoxicity mediated by cells from new onset patients was 34 +/- 2.4%, whereas in nondiabetic control subjects mean cytotoxicity was 25 +/- 1.8% (p less than 0.005). During remission, islet cytotoxicity returned to normal values in over half of the patients. There was no correlation between K562 and islet cell cytotoxicity in either of the latter two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗